Table 2.
Combination treatment of PNE and chemotherapy drugs or other compounds
| Combination | Extract type | Experimental model | Dose/Concentration | Anticancer activity | References |
|---|---|---|---|---|---|
| Seed of A. galanga, P. nigrum, C. aurantifolia, T. triandra, and C. sativa | Ethanolic extract | In vitro: Human colorectal cancer cells (SW620, HCT116), human lung cancer cells (A549, NCI-H460) | IC50 = 12.15–19.72 µg/mL | Exhibited antiproliferative and antimigration activities | [86] |
| Seed of P. nigrum and root bark of A. indica | Combination of methanolic extracts | In vitro: Epidermoid carcinoma cell line (A431) | IC50 = 208 µg/mL | Inhibited cancer cell proliferation | [87] |
| Dried fruits of P. nigrum and doxorubicin | Piperine-Free P. nigrum extract (PFPE) + doxorubicin | In vivo: NMU-induced mammary tumor in female Sprague Dawley rats | Dose = 200 mg/kg BW | PFPE did not affect doxorubicin's anticancer properties; suppressed cancer-related cytokines; reduced immune side effects | [27] |
| Dried fruits of P. nigrum and extracts from: A. paniculata, Z. spina-christi, G. extensum | PFPE + dichloromethane extracts | In vitro: colorectal adenocarcinoma (HT-29), colorectal cancer (SW620), breast cancer (MCF-7), ovarian cancer (A2780) | IC50 = 8.82–21.12 µg/mL | Antagonism with A. paniculata (HT-29, SW620, MCF-7); Synergy with Z. spina-christi in MCF-7; Apoptosis induction | [88] |
| Plant extract of O. sanctum and P. nigrum | Combination of aqueous extracts | In vitro: human breast cancer (MCF-7); In silico: ADMET analysis | IC50 = 78.61 µg/mL (combination) | Synergistic inhibition of cell proliferation, Apoptosis induction, ADMET properties for eugenol and piperine | [89] |
| Dried black pepper and doxorubicin | Ethanolic extract + doxorubicin | In vitro: Hamster ovary (CHO-K1) cells | IC50 = 8.5 µg/mL | Synergistic activity with doxorubicin; Enhanced efficacy and antigenotoxic effect; protection against genotoxicity | [91] |
| Stem of P. nigrum and paclitaxel | Ethanolic extract + paclitaxel | In vitro: paclitaxel-resistant cervical cancer cells (HeLa/PTX) | IC50 = 5.61–33.2 µM | Improved anticancer effect; enhanced apoptosis in resistant cancer cells | [92] |
| Black peppercorn of P. nigrum with turmeric or doxorubicin | PFPE + turmeric; PFPE + doxorubicin; PFPE + turmeric + doxorubicin | In vivo: NMU-induced mammary tumors in rats | PFPE-CH Dose = 100 mg/kg BW Turmeric Dose = 25 mg/kg BW | PFPE + turmeric/doxorubicin increased oxidative stress (TBARS); inhibited tumor growth; PFPE + turmeric enhanced IL-10 | [25] |
IC50: half-maximal inhibitory concentration; PFPE: Piperine-free P. nigrum extract; PTX: paclitaxel; NK: natural killer; ADMET: absorption: distribution: metabolism: excretion: and toxicity; NMU: N-nitroso-N-methylurea; BPE: black pepper extract