Harnessing the Bioactive Potential of Calotropis gigantea and Calotropis procera

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Year : 2026 | Volume : 04 | 02 | Page :
By

Ashutosh Shukla,

Shashikant Verma,

Bechan Sharma,

Neerja Shukla,

  1. Research Scholar, Department of Chemistry, Nari Shiksha Niketan P.G. College, Kaiserbagh, Lucknow, UP, India, Uttar Pradesh, India
  2. Research Scholar, Department of Chemistry, Nari Shiksha Niketan P.G. College, Kaiserbagh, Lucknow, UP, India, Uttar Pradesh, India
  3. Professor, Department of Biochemistry, University of Allahabad, Prayagraj, UP, India, Uttar Pradesh, India
  4. Assistant Professor, Department of Chemistry, Nari Shiksha Niketan P.G. College, Kaiserbagh, Lucknow, UP, India, Uttar Pradesh, India

Abstract

The medicinal plants of the Apocynaceae family Calotropis gigantea and Calotropis procera have gained more and more interest as source of bioactive molecules for biomedical applications like cancer therapy. They have various pharmacological activities, which are believed to be linked to various phytochemical constituents such as cardenolides, cardiac glycosides, flavonoids, triterpenoids, steroids, phenolic compounds, alkaloids, and proteins in their latex. The recent molecular and cellular studies show that extracts and isolated constituents of these plants have the potential to disrupt various processes associated with cancer initiation and progression such as production of reactive oxygen species (ROS), mitochondrial dysfunction, induction of apoptosis, arrest of cell cycle and disruption of major signaling pathways. Extracts of C. gigantea have been shown to cause cytotoxic effects on non-small-cell lung cancer cells via both intrinsic and extrinsic apoptotic pathway activation, as well as ROS generation and suppression of the proliferation of tumor cells. Its stem bark extract has also been shown to increase the cytotoxic activity of 5-fluorouracil in colon cancer cells via increased oxidative stress, ATP depletion, mitochondrial dysfunction and apoptosis. Likewise, extracts of C. procera exhibited cytotoxic activity in both MCF-7 breast cancer and HCT-116 colon cancer cell lines, and affected the cell cycle as well as proteins linked to the Akt/mTOR, CDK1/cyclin B1, and survivin-associated pathways. The results also show that C. procera cardenolides can be biotransformed to produce derivatives with improved cytotoxicity against breast cancer cells. In addition to direct plant extract, Calotropis mediated synthesis of metallic and metal oxide nanoparticles can also be considered as other therapeutic platform, which has been reported as anticancer, antimicrobial and anti inflammatory potential. Although these molecular effects are promising, there are many challenges such as toxicity, dose optimization, bioavailability and limited clinical evidence. Future studies should try to combine molecular pharmacology, omics techniques, computational drug discovery, nanotechnology-based delivery and clinical validation for the establishment of compounds derived from Calotropis as safe and effective therapeutic candidates.

Keywords: Calotropis gigantea; Calotropis procera; anticancer therapy; molecular signaling; cardenolides; apoptosis; cell-cycle arrest; ROS; Akt/mTOR; and nanotechnology; targeted drug delivery.

How to cite this article: Ashutosh Shukla, Shashikant Verma, Bechan Sharma, Neerja Shukla. Harnessing the Bioactive Potential of Calotropis gigantea and Calotropis procera. International Journal of Molecular Biotechnological Research. 2026; 04(02):-.
How to cite this URL: Ashutosh Shukla, Shashikant Verma, Bechan Sharma, Neerja Shukla. Harnessing the Bioactive Potential of Calotropis gigantea and Calotropis procera. International Journal of Molecular Biotechnological Research. 2026; 04(02):-. Available from: https://journals.stmjournals.com/ijmbr/article=2026/view=258271

References

(1) Winitchaikul T, Sawong S, Surangkul D, Srikummool M, Somran J, Pekthong D, Kamonlakorn K, Nangngam P, Parhira S, Srisawang P. Calotropis gigantea stem bark extract induced apoptosis related to ROS and ATP production in colon cancer cells. PLoS One. 2021 Aug 3;16(8):e0254392.

(2) Mutiah R, Sukardiman S, Widyawaruyanti A, Zulaikah S. Comparison of ethanol extract from roots, leaves, and flowers of Calotropis gigantea as anticancer on T47D breast cancer cell lines. ALCHEMY: Journal of Chemistry. 2016;5(1):1-4.

(3) Saddiq AA, Tag HM, Doleib NM, Salman AS, Hagagy N. Antimicrobial, antigenotoxicity, and characterization of Calotropis procera and its rhizosphere-inhabiting actinobacteria: in vitro and in vivo studies. Molecules. 2022 May 13;27(10):3123.

(4) Kiran RK, Vinod RR, Amol RK. Biotransformation of Cardenolides from Calotropis procera and Their Cytotoxic Potential against Human Mammary Gland Carcinoma Cells. Agricultural Science Digest. 2024 Oct 1;44(5):930.

(5) Lee J, Jang HJ, Chun H, Pham TH, Bak Y, Shin JW, Jin H, Kim YI, Ryu HW, Oh SR, Yoon DY. Calotropis gigantea extract induces apoptosis through extrinsic/intrinsic pathways and reactive oxygen species generation in A549 and NCI-H1299 non-small cell lung cancer cells. BMC complementary and alternative medicine. 2019 Jun 18;19(1):134.

(6) Lee J, Jang HJ, Chun H, Pham TH, Bak Y, Shin JW, Jin H, Kim YI, Ryu HW, Oh SR, Yoon DY. Calotropis gigantea extract induces apoptosis through extrinsic/intrinsic pathways and reactive oxygen species generation in A549 and NCI-H1299 non-small cell lung cancer cells. BMC complementary and alternative medicine. 2019 Jun 18;19(1):134.

(7) Olajuyin AM, Olajuyin AK, Wang Z, Zhao X, Xu Z, Zhang Q, Zhang X. Anti-proliferative, antioxidant effects of methanol extract of Calotropis procera leaf on lung cancer cells (H1299) and its ameliorative effect on expression of CD146 on blood cells. Clinical Phytoscience. 2021 Jun 7;7(1):51.

(8) Malhab LJ, Bajbouj K, Shehab NG, Elayoty SM, Sinoj J, Adra S, Taneera J, Saleh MA, Abdel-Rahman WM, Semreen MH, Alzoubi KH. Potential anticancer properties of calotropis procera: An investigation on breast and colon cancer cells. Heliyon. 2023 Jun 1;9(6).

(9) Mutiah R, Widyawaruyanti A, Sukardiman S. Calotropis gigantea leaf extract increases the efficacy of 5-fluorouracil and decreases the efficacy of doxorubicin in Widr colon cancer cell culture. Journal of Applied Pharmaceutical Science. 2018;8(4):51-6.

(10) Sawong S, Pekthong D, Suknoppakit P, Winitchaikul T, Kaewkong W, Somran J, Intapa C, Parhira S, Srisawang P. Calotropis gigantea stem bark extracts inhibit liver cancer induced by diethylnitrosamine. Scientific reports. 2022 Jul 15;12(1):12151.

(11) Rajkovic J, Novakovic R, Grujic-Milanovic J, Ydyrys A, Ablaikhanova N, Calina D, Sharifi-Rad J, Al-Omari B. An updated pharmacological insight into calotropin as a potential therapeutic agent in cancer. Frontiers in Pharmacology. 2023 Apr 17;14:1160616.

(12) Sun M, Pan D, Chen Y, Li Y, Gao K, Hu B. Coroglaucigenin enhances the radiosensitivity of human lung cancer cells through Nrf2/ROS pathway. Oncotarget. 2017 Mar 22;8(20):32807.

(13) Keiser, J.; Koch, V.; Deckers, A.; Cheung, H. T. A.; Jung, N.; Bräse, S. Naturally Occurring Cardenolides Affecting Schistosoma mansoni. ACS Infect Dis 2020, 6 (7), 1922-1927. DOI: 10.1021/acsinfecdis.0c00175 From NLM.

(14) Florkiewicz RZ, Anchin J, Baird A. The inhibition of fibroblast growth factor-2 export by cardenolides implies a novel function for the catalytic subunit of Na+, K+-ATPase. Journal of Biological Chemistry. 1998 Jan 2;273(1):544-51.

(15) Gobinath P, Packialakshmi P, Hatamleh AA, Al-Dosary MA, Al-Wasel YA, Balasubramani R, Surendrakumar R, Idhayadhulla A. Calotropis gigantea Assisted Synthesis of Zinc Oxide Nanoparticle Catalysis: Synthesis of Novel 3‐Amino Thymoquinone Connected 1, 4‐Dihyropyridine Derivatives and Their Cytotoxic Activity. Journal of Nanomaterials. 2022;2022(1):9697057.

(16) Rajkuberan C, Sudha K, Sathishkumar G, Sivaramakrishnan S. Antibacterial and cytotoxic potential of silver nanoparticles synthesized using latex of Calotropis gigantea L. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2015 Feb 5;136:924-30.

(17) El-Fitiany RA, AlBlooshi A, Samadi A, Khasawneh MA. Biogenic synthesis and physicochemical characterization of metal nanoparticles based on Calotropis procera as promising sustainable materials against skin cancer. Scientific reports. 2024 Oct 24;14(1):25154.

(18) Adabavazeh F, Pourseyedi S, Nadernejad N, Razavizadeh R, Mozafari H. Evaluation of synthesized magnetic nanoparticles and salicylic acid effects on improvement of antioxidant properties and essential oils of Calotropis procera hairy roots and seedlings. Plant Cell, Tissue and Organ Culture (PCTOC). 2022 Oct;151(1):133-48.

(19) Rabelo AC, Miglino MA, Arbizu S, Carreira AC, Filho AJ, Carneiro FJ, Layosa MA, Noratto G. Calotropis procera induced caspase-dependent apoptosis and impaired Akt/mTOR signaling in 4T1 breast cancer cells. Anti-Cancer Agents in Medicinal Chemistry-Anti-Cancer Agents). 2022 Nov 1;22(18):3136-47.

(20) Singh P, Dhole B, Choudhury J, Tuli A, Pandey D, Velpandian T, Gupta S, Chaturvedi PK. Calotropis procera extract inhibits prostate cancer through regulation of autophagy. Journal of Cellular and Molecular Medicine. 2024 Mar;28(6):e18050.

(21) Khan MF, Alanazi RF, Baabbad AA, Almoutiri ND, Wadaan MA. Angiogenic protein profiling, phytochemical screening and in silico anti-cancer targets validation of stem, leaves, fruit, and seeds of Calotropis procera in human liver and breast cancer cell lines. Environmental Research. 2024 Sep 1;256:119180.

(22) Kumari P, Panda PK, Jha E, Kumari K, Nisha K, Mallick MA, Verma SK. Mechanistic insight to ROS and apoptosis regulated cytotoxicity inferred by green synthesized CuO nanoparticles from Calotropis gigantea to embryonic zebrafish. Scientific reports. 2017 Nov 24;7(1):16284.

(23) Lee J, Jang H, Bak Y, Shin JW, Jin H, Kim YI, Won Ryu H, Ryang Oh S, Yoon DY. Calotropis gigantea extract induces apoptosis through extrinsic/intrinsic pathways and upregulation of reactive oxygen species in non-small-cell lung cancer cells. BioRxiv. 2018 Oct 11:441162.

(24) Khosravi Z, Kumar AH. Pharmacognosy and pharmacology of Calotropis gigantea for discovery of anticancer therapeutics.

(25) Sawong S, Pekthong D, Suknoppakit P, Winitchaikul T, Kaewkong W, Somran J, Intapa C, Parhira S, Srisawang P. Calotropis gigantea stem bark extracts inhibit liver cancer induced by diethylnitrosamine. Scientific reports. 2022 Jul 15;12(1):12151.

(26) Yadav, M.; Sarita, K.; Rai, K.; Yadav, A. Phytochemistry and Pharmacological Potential of Calotropis gigantea: A Comprehensive Review. International Journal of Pharmacy and Pharmaceutical Research 2025, 31, 2349-7203.

(27) Batool H, Hussain M, Hameed M, Ahmad R. A review on Calotropis procera its phytochemistry and traditional uses. Big Data Agric. 2020 Jan;2(2):56-8.

(28) Kumar G, Karthik L, Rao KV. A review on pharmacological and phytochemical profile of Calotropis gigantea Linn. Pharmacologyonline. 2011;1:1-8.

(29) Bandgar SA, Jadhav NR, Manjappa AS. A remarkable in vitro cytotoxic, cell cycle arresting and proapoptotic characteristics of low-dose mixed micellar simvastatin combined with alendronate sodium. Drug delivery and translational research. 2020 Aug;10(4):1122-35.

(30) Ahmed K, Tabuchi Y, Kondo T. Hyperthermia: an effective strategy to induce apoptosis in cancer cells. Apoptosis. 2015 Nov;20(11):1411-9.

(31) Saleem A, Akhtar MF, Sharif A, Akhtar B, Siddique R, Ashraf GM, Alghamdi BS, Alharthy SA. Anticancer, cardio-protective and anti-inflammatory potential of natural-sources-derived phenolic acids. Molecules. 2022 Oct 26;27(21):7286.

(32) Awad AB, Williams H, Fink CS. Effect of phytosterols on cholesterol metabolism and MAP kinase in MDA-MB-231 human breast cancer cells. The Journal of nutritional biochemistry. 2003 Feb 1;14(2):111-9.

(33) Russo GL, Russo M, Spagnuolo C, Tedesco I, Bilotto S, Iannitti R, Palumbo R. Quercetin: a pleiotropic kinase inhibitor against cancer. Advances in nutrition and cancer. 2013 Oct 11:185- 205.

(34) Lee CG, Kwon HK, Ryu JH, Kang SJ, Im CR, II Kim J, Im SH. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity. BMC Complementary and Alternative Medicine. 2010 Oct 20;10(1):60.

(35) Lin SZ, Wei WT, Chen H, Chen KJ, Tong HF, Wang ZH, Ni ZL, Liu HB, Guo HC, Liu DL. Antitumor activity of emodin against pancreatic cancer depends on its dual role: promotion of apoptosis and suppression of angiogenesis.

(36) Gera M, Patil AS, Bhosale V. Proliferating cell nuclear antigen: a novel growth and therapeutic biomarker. Clinical & Translational Metabolism. 2024 Aug 20;22(1):7.

(37) Pattani VP, Shah J, Atalis A, Sharma A, Tunnell JW. Role of apoptosis and necrosis in cell death induced by nanoparticle-mediated photothermal therapy. Journal of Nanoparticle Research. 2015 Jan;17(1):20.

(38) Elkady AI. Crude alkaloid extract of Rhazya stricta inhibits cell growth and sensitizes human lung cancer cells to cisplatin through induction of apoptosis. Genetics and molecular biology. 2013 Feb 1;36(1):12-21.

(39) Bose D, Olorunlana A, Abdel-Latif R, Famurewa AC, Othman EM. Virgin coconut oil and its lauric acid, between anticancer activity and modulation of chemotherapy toxicity: A review. Journal of Xenobiotics. 2025 Aug 5;15(4):126.

(40) Anupama N, Rani MP, Shyni GL, Raghu KG. Glucotoxicity results in apoptosis in H9c2 cells via alteration in redox homeostasis linked mitochondrial dynamics and polyol pathway and possible reversal with cinnamic acid. Toxicology in Vitro. 2018 Dec 1;53:178-92.

[41] Chaudhary AK, Yadav N, Bhat TA, O’Malley J, Kumar S, Chandra D. A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy. Drug discovery today. 2016 Jan 1;21(1):38-47.


Ahead of Print Subscription Review Article
Volume 04
02
Received 26/08/2026
Accepted 02/09/2026
Published 12/09/2026
Publication Time 17 Days


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