
CLC number:
On-line Access: 2025-11-19
Received: 2024-09-19
Revision Accepted: 2024-12-03
Crosschecked: 2025-11-19
Cited: 0
Clicked: 1615
Sinan TETIKOGLU, Muharrem AKCAN, Ugur UZUNER, Selcen CELIK UZUNER. Selective anastasis induction by bee venom in normal cells: a promising strategy for breast cancer therapy with minimal impact on cell viability[J]. Journal of Zhejiang University Science B, 2025, 26(11): 1121-1131.
@article{title="Selective anastasis induction by bee venom in normal cells: a promising strategy for breast cancer therapy with minimal impact on cell viability",
author="Sinan TETIKOGLU, Muharrem AKCAN, Ugur UZUNER, Selcen CELIK UZUNER",
journal="Journal of Zhejiang University Science B",
volume="26",
number="11",
pages="1121-1131",
year="2025",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2400466"
}
%0 Journal Article
%T Selective anastasis induction by bee venom in normal cells: a promising strategy for breast cancer therapy with minimal impact on cell viability
%A Sinan TETIKOGLU
%A Muharrem AKCAN
%A Ugur UZUNER
%A Selcen CELIK UZUNER
%J Journal of Zhejiang University SCIENCE B
%V 26
%N 11
%P 1121-1131
%@ 1673-1581
%D 2025
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2400466
TY - JOUR
T1 - Selective anastasis induction by bee venom in normal cells: a promising strategy for breast cancer therapy with minimal impact on cell viability
A1 - Sinan TETIKOGLU
A1 - Muharrem AKCAN
A1 - Ugur UZUNER
A1 - Selcen CELIK UZUNER
J0 - Journal of Zhejiang University Science B
VL - 26
IS - 11
SP - 1121
EP - 1131
%@ 1673-1581
Y1 - 2025
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2400466
Abstract: anastasis is a phenomenon described as a cellular escape from ethanol-induced cell death. Although the relevant mechanism has not yet been fully elucidated, anastasis is thought to play a role in drug resistance in cancer cells. To date, the regulation of anastasis in normal and cancerous cells has not been clarified. The current cancer treatment strategies are expected to selectively attack cancer cells without negatively affecting normal cell proliferation. Inspired by the anti-cancer potential of bee venom, this study is the first to evaluate whether bee venom has similar selectivity in producing an anastatic effect. The results indicated that bee venom induces anastasis in normal cells (Michigan cancer Foundation-10A (MCF10A), Adult Retinal Pigment Epithelium cell line-19 (ARPE-19), and National Institutes of Health 3T3 cell line (NIH3T3)) but causes irreversible cell death in breast cancer cells (M.D. Anderson-Metastatic Breast-231 (MDA-MB-231) and Michigan cancer Foundation-7 (MCF7)). Liver cancer (HepG2) cells were moderately more resistant to permanent cell death after bee venom treatment compared to breast cancer cells. However, cisplatin caused permanent non-selective cell death in both normal and cancerous cells. The selectivity indices after bee venom treatment were higher compared to cisplatin. Taken together, bee venom was shown to induce selective anastasis only in normal cells, not in cancer cells, which suggests that bee venom has significant potential in selective cancer therapy, especially for breast cancer, via promoting the recovery and maintenance of viability of normal cells.
[1]AllisonSJ, SadiqM, BaronouE, et al., 2017. Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands. Cancer Lett, 403:98-107.
[2]BaracchiD, TurillazziS, 2010. Differences in venom and cuticular peptides in individuals of Apis mellifera (Hymenoptera: Apidae) determined by MALDI-TOF MS. J Insect Physiol, 56(4):366-375.
[3]Ben HassenM, MsalbiD, JismyB, et al., 2023. Three component one-pot synthesis and antiproliferative activity of new [1,2,4]triazolo[4,3-a]pyrimidines. Molecules, 28(9):3917.
[4]BritoAF, AbrantesAM, Pinto-CostaC, et al., 2012. Hepatocellular carcinoma and chemotherapy: the role of p53. Chemotherapy, 58(5):381-386.
[5]CuiZY, ZhouZG, SunZY, et al., 2024. Melittin and phospholipase A2: promising anti-cancer candidates from bee venom. Biomed Pharmacother, 179:117385.
[6]da Cunha RecueroS, VianaNI, ReisST, et al., 2024. Phospholipase A2 expression in prostate cancer as a biomarker of good prognosis: a comprehensive study in patients with long follow-up. Urologia, 91(4):720-726.
[7]DemirbağB, BüyükafşarK, KayaH, et al., 2024. Investigation of the anticancer effect of newly synthesized palladium conjugate schiff base metal complexes on non-small cell lung cancer cell line and mouse embryonic fibroblast cell line. Biochem Biophys Res Commun, 735:150658.
[8]el SharkawiFZ, SalehSS, el SayedAFM, 2015. Potential anti cancer activity of snake venom, bee venom and their components in liver and breast carcinoma. Int J Pharm Sci Res, 6(8):3224-3235.
[9]Göker BağcaB, 2022. Identification of the phenomenon of anastasis in breast cancer cells. Ege Tıp Dergisi, 61(3):387-396.
[10]HollanderT, AeedPA, ElhammerAP, 1993. Characterization of the oligosaccharide structures on bee venom phospholipase A2. Carbohydr Res, 247:291-297.
[11]HonariP, ShahbazzadehD, BehdaniM, et al., 2024. Highly in vitro anti-cancer activity of melittin-loaded niosomes on non-small cell lung cancer cells. Toxicon, 241:107673.
[12]KashyapD, BhattacharyaS, IrinikeS, et al., 2024. Cancer associated fibroblasts modulate the cytotoxicity of anti-cancer drugs in breast cancer: an in vitro study. Breast Dis, 43:25-36.
[13]KntayyaSB, Din IbrahimM, AinNM, et al., 2018. Induction of apoptosis and cytotoxicity by isothiocyanate sulforaphene in human hepatocarcinoma HepG2 cells. Nutrients, 10(6):718.
[14]KubelkaV, AltmannF, StaudacherE, et al., 1993. Primary structures of the N-linked carbohydrate chains from honeybee venom phospholipase A2. Eur J Biochem, 213(3):1193-1204.
[15]LeeHL, ParkSH, KimTM, et al., 2015. Bee venom inhibits growth of human cervical tumors in mice. Oncotarget, 6(9):7280-7892.
[16]LiuX, ChenDW, XieLP, et al., 2002. Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in-vitro and growth of murine B16 melanomas in-vivo. J Pharm Pharmacol, 54(8):1083-1089.
[17]MizielskaA, DziechciowskaI, SzczepańskiR, et al., 2023. Doxorubicin and cisplatin modulate miR-21, miR-106, miR-126, miR-155 and miR-199 levels in MCF7, MDA-MB-231 and SK-BR-3 cells that makes them potential elements of the DNA-damaging drug treatment response monitoring in breast cancer cells—a preliminary study. Genes, 14(3):702.
[18]OršolićN, ŠverL, VerstovšekS, et al., 2003. Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom. Toxicon, 41(7):861-870.
[19]SaydamF, NalkiranHS, 2021. Anticancer effects of a novel herbal combination as a potential therapeutic candidate against lung cancer. Eur J Integr Med, 48:101401.
[20]SeerviM, SumiS, ChandrasekharanA, et al., 2019. Molecular profiling of anastatic cancer cells: potential role of the nuclear export pathway. Cell Oncol, 42(5):645-661.
[21]Sevim NalkiranH, YildizDA, SaydamF, et al., 2023. Targeting the anaphase-promoting complex/cyclosome (APC/C) enhanced antiproliferative and apoptotic response in bladder cancer. Saudi J Biol Sci, 30(3):103564.
[22]TangHL, YuenKL, TangHM, et al., 2009. Reversibility of apoptosis in cancer cells. Br J Cancer, 100:118-122.
[23]TangHL, TangHM, MakKH, et al., 2012. Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response. Mol Biol Cell, 23(12):2240-2252.
[24]TangHM, TalbotCC, FungMC, et al., 2022. Transcriptomic study of anastasis for reversal of ethanol-induced apoptosis in mouse primary liver cells. Sci Data, 9:418.
[25]TuWC, WuCC, HsiehHL, et al., 2008. Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells. Toxicon, 52(2):318-329.
[26]van VaerenberghM, DebyserG, DevreeseB, et al., 2014. Exploring the hidden honeybee (Apis mellifera) venom proteome by integrating a combinatorial peptide ligand library approach with FTMS. J Proteomics, 99:169-178.
[27]WangKL, TaoLC, ZhuMF, et al., 2024. Melittin inhibits colorectal cancer growth and metastasis by activating the mitochondrial apoptotic pathway and suppressing epithelial‒mesenchymal transition and angiogenesis. Int J Mol Sci, 25(21):11686.
[28]WangYX, WangR, LiuXH, et al., 2023. Chemotherapy-induced executioner caspase activation increases breast cancer malignancy through epigenetic de-repression of CDH12. Oncogenesis, 12:34.
[29]XieJ, ZhuL, YangXT, et al., 2024. Combination of theoretical analysis and experiments: exploring the role of PLA2G7 in human cancers, including renal cancer. Heliyon, 10(6):e27906
[30]ZhangXL, WeiK, MajdMH, et al., 2025. Investigating the cytotoxic, apoptotic, treatment-resistant, and inflammatory response properties of a gold(III) complex containing a tetradentate schiff base ligand. J Braz Chem Soc, 36(4):e-20240189.
Open peer comments: Debate/Discuss/Question/Opinion
<1>