# Investigating the Synergistic Effect of the Cannabis Extract PHEC-66 and Chemotherapeutic Agents on Human Melanoma Cells

**Authors:** Ava Bachari, Srinivasareddy Telukutla, Nazim Nazar, Terrence Jerald Piva, Nitin Mantri

PMC · DOI: 10.3390/ijms27041794 · 2026-02-13

## TL;DR

This study explores how combining a cannabis extract with chemotherapy drugs affects melanoma cells, finding both helpful and harmful interactions.

## Contribution

The study reveals both additive and antagonistic effects of combining PHEC-66 with chemotherapeutic agents in melanoma cells.

## Key findings

- PHEC-66 combined with docetaxel and auranofin showed a potential additive effect on melanoma cell viability.
- PHEC-66 with cisplatin had an antagonistic effect, reducing the drug's cytotoxicity.
- The results highlight the need for careful evaluation of drug combinations in melanoma treatment.

## Abstract

Melanoma is a malignant neoplasm that originates from melanocytes. It continues to pose a significant challenge in oncology due to its aggressive nature and limited treatment options. This study investigates the potential additive effects of PHEC-66, a cannabis extract, in combination with conventional chemotherapeutic agents auranofin, docetaxel, and cisplatin on the viability of a range of melanoma cell lines. These combinations were evaluated using the MTT assay on MM418-C1, MM329, C32, and D24 melanoma cells. There was a nuanced response observed when PHEC-66 was combined with docetaxel and auranofin in these cells, suggesting a potential additive effect. Contrastingly, the combination of PHEC-66 with cisplatin elicited an antagonistic effect, wherein the expected cytotoxicity of this drug was compromised. This unexpected interaction may stem from complex interplays between the agents that influence drug uptake, DNA damage response, and cell survival pathways. These findings underscore the importance of careful selection and assessment of drug combinations, as an additive effect and antagonistic interactions can significantly impact therapeutic outcomes. Further studies are warranted to elucidate the molecular mechanisms behind these interactions and to validate these observations using in vivo models.

## Linked entities

- **Chemicals:** auranofin (PubChem CID 16667669), docetaxel (PubChem CID 148124), cisplatin (PubChem CID 5460033)
- **Diseases:** melanoma (MONDO:0005105)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CNR1 (cannabinoid receptor 1) [NCBI Gene 1268] {aka CANN6, CB-R, CB1, CB1A, CB1K5, CB1R}, PRDX5 (peroxiredoxin 5) [NCBI Gene 25824] {aka ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, MTRF1 (mitochondrial translation release factor 1) [NCBI Gene 9617] {aka MRF1, MTTRF1, RF1}, CAT (catalase) [NCBI Gene 847], KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, GNAQ (G protein subunit alpha q) [NCBI Gene 2776] {aka CMAL, G-ALPHA-q, GAQ, SWS}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, GNA11 (G protein subunit alpha 11) [NCBI Gene 2767] {aka FBH, FBH2, FHH2, GNA-11, HG1K, HHC2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CDK6 (cyclin dependent kinase 6) [NCBI Gene 1021] {aka MCPH12, PLSTIRE}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CNR2 (cannabinoid receptor 2) [NCBI Gene 1269] {aka CB-2, CB2, CX5}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893] {aka ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6}, CUL1 (cullin 1) [NCBI Gene 8454], PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}
- **Diseases:** Cutaneous melanoma (MESH:C562393), depression (MESH:D003866), head and neck, lung, ovarian, leukemia, breast, brain, kidney, testicular, and skin cancers (MESH:D001943), cytotoxic (MESH:D064420), metastasis (MESH:D009362), head and neck squamous cell carcinoma (MESH:D000077195), vomiting (MESH:D014839), fatigue (MESH:D005221), skin cancer (MESH:D012878), hair loss (MESH:D000505), nausea (MESH:D009325), cancer (MESH:D009369), inflammatory (MESH:D007249), injury to (MESH:D014947), Melanoma (MESH:D008545)
- **Chemicals:** CBD (MESH:D002185), DMSO (MESH:D004121), Docetaxel (MESH:D000077143), ROS (MESH:D017382), Cannabinoids (MESH:D002186), nivolumab (MESH:D000077594), taxane (MESH:C080625), lipid (MESH:D008055), dabrafenib (MESH:C561627), purine (MESH:C030985), endocannabinoid (MESH:D063388), glutathione (MESH:D005978), CO2 (MESH:D002245), Thiol (MESH:D013438), MTT (MESH:C070243), pembrolizumab (MESH:C582435), penicillin (MESH:D010406), 1-thio-beta-D-glucose tetraacetate (-), Cisplatin (MESH:D002945), ipilimumab (MESH:D000074324), Auranofin (MESH:D001310), trametinib (MESH:C560077), encorafenib (MESH:C000601108), streptomycin (MESH:D013307), vemurafenib (MESH:D000077484), THC (MESH:D013759), cobimetinib (MESH:C574276), dacarbazine (MESH:D003606), formazan (MESH:D005562), platinum (MESH:D010984), gold (MESH:D006046), Vitamin D (MESH:D014807)
- **Species:** Homo sapiens (human, species) [taxon 9606], Cannabis sativa (species) [taxon 3483], Mus musculus (house mouse, species) [taxon 10090], Human alphaherpesvirus 1 (Herpes simplex virus type 1, no rank) [taxon 10298]
- **Mutations:** V600R, BRAFV600E, V600D, (D) for 48
- **Cell lines:** Cat No C-12400 — Homo sapiens (Human), Transformed cell line (CVCL_R655), HEM — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_6D72), D24 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_W871), MM96L — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_D853), MCF7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), B16F10 — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_0159), C32 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_1097), MM418-C1 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_UM71), MM329 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_C838), PHEC-66 — Homo sapiens (Human), Transformed cell line (CVCL_6G48)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940197/full.md

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Source: https://tomesphere.com/paper/PMC12940197