Chemosensitizing activity of peptide from Lentinus squarrosulus (Mont.) on cisplatin-induced apoptosis in human lung cancer cells

AbstractThe limitations of cisplatin, a standard chemotherapy for lung cancer, have been documented with serious adverse effects and drug resistance. To address the need for novel therapy, this study firstly reveals the potential of peptide from Lentinus squarrosulus (Mont.) as a chemotherapeutic adjuvant for cisplatin treatment. The purified peptide from L. squarrosulus aqueous extracts was obtained after eluting with 0.4 M NaCl through FPLC equipped with anion exchange column. Preincubation for 24 h with 5 µg/mL of the peptide at prior to treatment with 5 µM cisplatin significantly diminished %cell viability in various human lung cancer cells but not in human dermal papilla and proximal renal cells. Flow cytometry indicated the augmentation of cisplatin-induced apoptosis in lung cancer cells pretreated with peptide from L. squarrosulus. Preculture with the peptide dramatically inhibited colony formation in lung cancer cells derived after cisplatin treatment. Strong suppression on integrin-mediated survival was evidenced with the diminution of integrins (β1, β3, β5, α5, αV) and down-stream signals (p-FAK/FAK, p-Src/Src, p-Akt/Akt) consequence with alteration of p53, Bax, Blc-2 and Mcl-1 in cisplatin-treated lung cancer cells preincubated with peptide from L. squarrosulus. These results support the development of L. squarrosulus peptide as a novel combined chemotherapy with cisplatin for lung cancer treatment.

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Fas Ligand Enhances Apoptosis of Human Lung Cancer Cells Cotreated with RIG-I-like Receptor Agonist and Radiation

Current Cancer Drug Targets ◽

10.2174/1568009620666200115161717 ◽

2020 ◽

Vol 20 (5) ◽

pp. 372-381

Author(s):

Yoshiaki Sato ◽

Hironori Yoshino ◽

Eichi Tsuruga ◽

Ikuo Kashiwakura

Keyword(s):

Lung Cancer ◽

Cell Surface ◽

Cancer Cells ◽

Fas Ligand ◽

Human Lung ◽

Lung Cancer Cells ◽

Poly I:C ◽

Human Lung Cancer ◽

Human Lung Cancer Cells ◽

Induced Apoptosis

Background: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play key roles in the antiviral response, but recent works show that RLR activation elicits anticancer activity as well, including apoptosis. Previously, we demonstrated that the anticancer activity of the RLR agonist Poly(I:C)-HMW/LyoVec™ [Poly(I:C)-HMW] against human lung cancer cells was enhanced by cotreatment with ionizing radiation (IR). In addition, cotreatment with Poly(I:C)-HMW and IR induced apoptosis in a Fas-independent manner, and increased Fas expression on the cell surface. Objective: The current study investigated the resultant hypothesis that Fas ligand (FasL) may enhance apoptosis in lung cancer cells cotreated with Poly(I:C)-HMW+IR. Methods: FasL was added into culture medium at 24 h following cotreatment with Poly(I:C)- HMW+IR, after upregulation of cell surface Fas expression on human lung cancer cells A549 and H1299 have already been discussed. Results: FasL enhanced the apoptosis of A549 and H1299 cells treated with Poly(I:C)-HMW+IR. Similarly, IR alone - and not Poly(I:C)-HMW - resulted in the upregulation of cell surface Fas expression followed by a high response to FasL-induced apoptosis, thus suggesting that the high sensitivity of cells treated with Poly(I:C)-HMW+IR to FasL-induced apoptosis resulted from the cellular response to IR. Finally, knockdown of Fas by siRNA confirmed that the high response of treated cells to FasL-induced apoptosis is dependent on Fas expression. Conclusion: In summary, the present study indicates that upregulated Fas expression following cotreatment with Poly(I:C)-HMW and IR is responsive to FasL-induced apoptosis, and a combination of RLR agonist, IR, and FasL could be a potential promising cancer therapy.

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