Endophytic fungi represent an important source of compounds with biological activity, such as phenolic acids, alkaloids, quinones, steroids, saponins, tannins, and terpenoids, which increases their potential in the identification of new compounds with antidiabetic, anti-inflammatory, antiviral, immunosuppressive, anti-arthritis, anti-oxidant, anti-microbial, and anti-cancer effects . However, only less than 16% of the fungal species described have been cultured and studied and less than 5% of the total fungal species that have been characterized represent an important source of bioactive metabolites . The distribution of certain populations of endophytic fungi is restricted to a species or family of plants, as well as to the genotype of the species, thus the presence of a specific population of fungi may determine the production of various secondary metabolites . Therefore, due to the vast number of plant species in the world, different strategies have been devised to select the plants from which to isolate endophytes with biological activity, including the use of plants that have been exploited for human use in traditional medicine , as well as those with special strategies for their survival or that grow in extreme environments . Plants that inhabit extreme environments, such as arid zones, are associated with endophytic fungi since they improve their performance and resistance against biotic and abiotic factors through the production of bioactive compounds . However, the biotechnological potential of fungi isolated from this type of environment is still limited . Therefore, this study reports for the first time the cytotoxic activity of endophytic fungi isolated from P. marginatus, a species of cactus endemic to Mexico, previously reported with anticancer activity [16–18]. In the present study, we isolated Penicillium, Aspergillus, and Cladosporium genera, which have been commonly isolated from plants that inhabit dry environments, such as cacti [19, 28, 29], whereas Metarhizium has been reported as a natural endophyte of legumes , conifers , herbs, and wildflowers . We then report for the first time the isolation of Metarhizium as an endophyte of cacti.
Currently, anticancer resistance is a serious problem in oncology as in the case of breast cancer , colon cancer , and Non-Hodgkin lymphoma . Therefore, it is essential to search and identify new compounds with antitumor activity, for which cancer cells are not resistant . Various endophytic fungi have shown anti-cancer effect against hepatoma (HepG2), lung cancer (A-549), colorectal cancer (HCT-116, HT-29), breast cancer (MCF7), ovarian cancer (SKVO3), leukemia (HL-60), carcinoma (KB), cervical cancer (Hela), and lymphoma (L5178Y) .
The isolated strains of P. citrinum PME-H001 and PME-H002, showed differential cytotoxic activity, which is consistent with other studies evidencing that the medicinal properties of endophytic fungi vary, despite they belong to the same genus and are isolated from the same host . On the other hand, the anticancer activity of this species has been reported against different tumor cell lines such as A549, Hela, HepG2, L5178Y, MOLT-4, MCF-7, BT-474, and MDA-MB-231, identifying different compounds responsible for the activity, such as penicillocitrin A, citriquinochroman, citrinin, scalusamide A, perinadine A, pencitrin, and pencitrinol [37–41].
Fungi of the genus Aspergillus are considered an important source of bioactive compounds with anticancer activity, among which are alkaloids, pyrones, polyketides, lactones, sterols, xanthones, anthraquinones, terpenes, peptides, depsipeptides, cyclic peptides, cytochalasins, enzymes, and proteins. They have been evaluated in different tumor cell lines such as MCF7, HL-60, K-562, A549, MOLT-4 and HEP-G2 . Furthermore, the potential of M. anisopliae to produce anti-cancer compounds such as taxol with yields of 846.1 µg/L in liquid medium has been previously demonstrated by others  and destruxin B with IC50 values of 4.9 𝜇M in A549 lung cancer cells .
Cladosporium sp. methanol extract caused the highest toxicity against MCF-7 cells, which agrees with a study reported by Raj et al.  showing the activity of taxol obtained from C. oxysporum extracts against the T47D breast cancer cell line, with an IC50 value of 2.5 µM, after 24 h of incubation.
Most anti-cancer drugs do not differentiate between tumor and normal cells, thus researchers investigate for new drugs that are selective for cancer cells, with minimal effects for other cells . However, some endophytic fungal extracts such as Acremonium sp. and Pestalotiopsis suffocata are toxic against PBMCs with IC50 values of 13.4 and 12.2 µg/ml .
Endophytic fungi may play an important role in providing chemotherapeutic compounds with high specificity and minimal side effects. Therefore, the search for endophytic fungi from different habitats may provide an excellent avenue to discover new drugs and their application in the medical area, for the control of different human diseases.