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Pomiferin, a natural prenylated flavonoid, modulates drug resistance
mechanisms and resensitizes multidrug-resistant cancer cells
1,2
1
,3
Ching-Hui Su, Chin-Chuan Hung, Y u -Hsuan Lan, Ching-I Hsu*
1
1 Department of Pharmacy, College of Pharmacy, China Medical University, Taichung
406040, Taiwan
2 Department of Pharmacy, China Medical University Hospital, Taichung 404327, Taiwan
3 Department of Pharmacy, China Medical University Beigang Hospital, Yunlin 651012,
Taiwan
* E-mail: 062897@tool.caaumed.org.tw
Abstract
Multidrug resistance (MDR) represents a significant obstacle in effective cancer treatment,
often leading to chemotherapy failure and disease progression. In the present study, we explored
the ability of pomiferin, a naturally derived prenylated flavonoid, to enhance the treatment
sensitivity of drug-resistant cancer cells. Human cancer cell lines, KB (drug-sensitive) and
KBvin (drug-resistant), were used to investigate the potential mechanisms by which pomiferin
overcomes drug resistance, through assessments of cytotoxicity, cell cycle distribution,
apoptosis, cell proliferation, and P-glycoprotein (P-gp)–related function using calcein-AM
uptake, ATPase activity, and MDR1 shift assays. The results revealed that pomiferin exhibited
notable cytotoxicity in both cell types, with enhanced sensitivity towards the MDR KBvin cells.
Flow cytometric analysis demonstrated that pomiferin alone induced G1/G0 phase arrest, while
its combination with paclitaxel significantly increased the sub-G1 population in the KBvin cells,
suggesting enhanced apoptotic activity, as further confirmed by apoptosis assay results.
Pomiferin also significantly inhibited MDR cancer cell proliferation. Further P-gp–related
assays suggested that pomiferin partially interferes with P-gp–mediated efflux, though its
activity does not appear to involve direct modulation of ATPase function. Overall, our findings
demonstrate that pomiferin enhances the response of drug-resistant cancer cells through
multiple mechanisms, including cell cycle modulation, apoptosis induction, and partial
engagement with drug resistance pathways. These results support the potential of pomiferin as
an adjuvant compound to improve the efficacy of chemotherapeutic agents in MDR cancer
treatment.
Keywords: Pomiferin; Cancer treatment; MDR cancer

