Piperlongumine induces apoptosis and autophagy via the PI3K/Akt/mTOR pathway in KB human cervical cancer cells

Eun-Ji Han; Eun-Young Choi; Su-Ji Jeon; Sang-Woo Lee; Jun-Mo Moon; Soo-Hyun Jung; Bumseok Kim; Sung-Dae Cho; Jeong-Seok Nam; Changsun Choi; Jeong-Hwan Che; Ji-Youn Jung

doi:10.1016/j.fct.2023.114051

Piperlongumine induces apoptosis and autophagy via the PI3K/Akt/mTOR pathway in KB human cervical cancer cells

Food Chem Toxicol. 2023 Oct:180:114051. doi: 10.1016/j.fct.2023.114051. Epub 2023 Sep 19.

Authors

Affiliations

¹ Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, 32439, Republic of Korea.
² College of Veterinary Medicine and Bio-Safety Research Institute, Jeonbuk National University, Iksan, 54596, Republic of Korea.
³ Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 03080, Republic of Korea.
⁴ School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
⁵ School of Food Science and Technology, Chung-ang University, Ansung, 17546, Republic of Korea.
⁶ Biomedical Center for Animal Resource Development, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea; Biomedical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
⁷ Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, 32439, Republic of Korea; Research Institute for Natural Products, Kongju National University, Yesan, 32439, Republic of Korea. Electronic address: wangza@kongju.ac.kr.

PMID: 37734464
DOI: 10.1016/j.fct.2023.114051

Abstract

Natural products are continuously being researched to develop safe and effective treatment options for cervical cancer, the fourth most common cancer in women. Piperlongumine (PL), an amide alkaloid mainly present in long pepper, exhibits neuroprotective and anti-cancer properties. However, the specific effect of PL in cervical cancer and the relationship between the anti-cancer pathway and autophagy remain unclear. Therefore, we aimed to investigate PL-induced apoptosis in KB human cervical cancer cells and the relationship between apoptosis and autophagy therein. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound-healing assays showed that PL treatment suppressed KB cell viability and proliferation. Apoptosis was identified through 4',6-diamidino-2-phenylindole and annexin V-propidium iodide staining, increased cleaved-poly (ADP-ribose) polymerase and Bcl-2 associated X levels, and decreased B cell lymphoma 2 levels. Acridine orange staining and increased microtubule-associated protein 1A/1B-light chain 3-II and Beclin-1 levels confirmed autophagy. We determined that KB cell-related autophagy exerted cytoprotective effects using the autophagy inhibitors 3-methyladenine and hydroxychloroquine. PL treatment promoted apoptosis by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in KB cells; inhibiting the pathway using PI3K inhibitors increased autophagy. We suggest that PL is a potential natural anticancer agent for cervical cancer treatment.

Keywords: Anticancer effects; Apoptosis; Autophagy; Cervical cancer; PI3K/Akt/mTOR pathway; Piperlongumine.