A short history of plants and humans

Humans have used plants as food and natural medicines since the beginning of time. Interestingly, medicinal plants have been and continue to be used as a medicinal resource in almost all cultures around the world (the exception may be, for example, the Inuit, whose ice gardens may not be best suited to growing chamomile, for example). IAt this point it is worth mentioning that the path to discovering the correct use of particular plants was through trial and error, that is, often at the expense of the potential discoverer’s health and life. Fortunately, thanks to the development of civilization and research methods, today’s pharmacy does not rely on such risky methods, but on proven medicinal substances in standardized doses, without the further need to sacrifice individuals from the human population [1]. 

The advantage of in vitro culture over traditional plant cultivation

It is worth realizing where the current direction to conduct in vitro plant culture in the context of the pharmaceutical industry came from.  The answer is relatively simple – particular environmental variables (day/night ratio, temperature, water, salinity, soil composition) affect the accumulation of plant secondary metabolites in the plant [2]. That is, to put it briefly and slightly abstractly – chamomile tea harvested in the eastern part of the Earth’s hemisphere will differ from that harvested and brewed in the west in terms of the quantity and quality of active substances (most likely, because there will always be that one wayward chamomile that won’t). This is because plants synthesize different metabolites in response to the environmental stresses they are subjected to [2]. Thanks to the fact that in vitro culture can be based on genetic clones of individual plant tissues, we have the possibility of obtaining an identical profile and content of secondary metabolites. This property is extremely important for standardizing the extraction of plant extracts or final purified active compounds [3].

Research by Polish Scientists on the efficacy of Carpesium divaricatum

Researchers from the Jerzy Maj Institute of Pharmacology of the Polish Academy of Sciences and the Jagiellonian University of Krakow undertook a comparison of the cytotoxic activity of extracts from plant tissues cultured in vitro and classic cultivation. The study was performed on a species of Carpesium divaricatum (no, it’ is not a variety of chamomile), and the extracts were tested on both cancerous and healthy cell lines¹. The cytotoxic effects of the extracts were mainly based on compounds from the terpenoid subgroup of sesquiterpene lactones, specifically germacranolides [4,5].

Although most in vitro plantings of C. divaricatum accumulated smaller amounts of germacranolide than leaves of plants grown in the ground, one culture with two growth factors (6-benzyladenine and 1-naphthaleneacetic acid) allowed the same accumulation of germacranolide as in leaves of conventionally grown plants [4]. 

The cell lines used to evaluate the cytotoxicity of the extracts were compiled into 3 groups based on their origin: prostate, skin and gastrointestinal. Each group contained two lines derived from cancer cells and one healthy line of similar origin [4]. 

It is noteworthy that the extracts of different origins showed different specificity against cancer cells especially in the group of gastrointestina and skin cell lines, however they were quite specific towards the tumor cells. As for prostate cell lines, they showed poor selectivity and also affected non-cancerous cells [4]. 

In conclusion, the studies cited above provide the basis for a more standardized use of plant extracts in the pharmaceutical industry. Despite the use of in vitro plant cultures, extracts from cultured tissues retained selective cytotoxic effects on individual cancer cell lines, producing effects similar to extracts obtained from conventionally cultured plants.

From scientific to ours – a brief, colloquial summary for non-scientific readers 

Polish Scientists from Krakow compared extracts (such a tincture, only in this case on acetone) from plant tissues raised in vitro (so-called “from a test tube”) of a certain plant species against extracts from plants traditionally harvested from the soil. The right combination of the form of the substrate ( in this case liquid – “pieces” of the plant are grown on certain thick liquid) with growth factors ( substances added externally to force the plant to grow faster) managed to obtain similar values of active compounds (this is what works in the extract). It turned out that in the healthy/cancerous cell comparison, the active substances from the extracts were more likely to damage cancer cells, despite subjecting the lines to the same conditions.  This is promising, due to the fact that current attempts to create cancer therapies are based on selectivity – that is, on “smart substances” that won’t attack “everything as it flies,” but instead target altered tissues directly. 

Author’s comments:

Because of how hopeful cancer research is, it is worth highlighting a couple of points:

¹ There have been no randomized human clinical trials on this plant to date demonstrating the plant’s anti-cancer effects, moreover, there have been few animal studies, and if there have been they have been of low quality (reference to the cited example: [6]). This does not mean that the compound does not have anticancer properties – the point is to draw attention to the need for further research into the safety and efficacy of the extract of this plant and to prevent its use “on its own”.

^2. As for the cells of the gastrointestinal tract, strictly healthy cells were not taken, and were replaced by a liver cancer cell line. The authors say that this is a standard method to help assess the hepatotoxicity of the extracts used.

Bibliography: 

[1] Medicinal plants: Past history and future perspective – Jamshidi-Kia Fatemeh, Lorigooini Zahra, Amini-Khoei Hossein (2018), Herbmed Pharmacol, http://herbmedpharmacol.com/Article/jhp-1198

[2] The Influence of Environmental Conditions on Secondary Metabolites in Medicinal Plants: A Literature Review – Poonam Pant, Sudip, Pandey, Stefano Dall’Acqua (2021), Chemistry & Biodiversity. https://onlinelibrary.wiley.com/doi/full/10.1002/cbdv.202100345

[3] In vitro plant tissue culture: means for production of biological active compounds – Espinosa-Leal, C.A., Puente-Garza, C.A. & García-Lara, S. (2018). Planta 248, 1–18.  https://doi.org/10.1007/s00425-018-2910-1

[4] Chemical Composition and Cytotoxic Activity of Extracts from Carpesium divaricatum: In Vitro- versus Field-Grown Plants – Malarz J, Galanty A, Stojakowska A. (2022). Plants (Basel). doi: https://doi.org/10.3390/plants11212815.

[5] . Applications of Sesquiterpene Lactones: A Review of Some Potential Success Cases – Moujir, L.; Callies, O.; Sousa, P.M.C.; Sharopov, F.; Seca, A.M.L. (2020) Appl. Sci. https://doi.org/10.3390/app10093001https://www.mdpi.com/2076-3417/10/9/3001

[6] A natural compound derivative P-13 inhibits STAT3 signaling by covalently inhibiting Janus kinase 2 – Huang, H., Niu, J., Wang, F. et al. (2019). Invest New Drugs 37, 452–460